論文 - 詳細
RRC ID | 62695 |
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著者 | Ueta H, Xu XD, Yu B, Kitazawa Y, Yu E, Hara Y, Morita-Nakagawa M, Zhou S, Sawanobori Y, Ueha S, Rokutan K, Tanaka T, Tokuda N, Matsushima K, Matsuno K. |
タイトル | Suppression of liver transplant rejection by anti-donor MHC antibodies via depletion of donor immunogenic dendritic cells. |
ジャーナル | Int Immunol |
Abstract |
BACKGROUND:We previously found two distinct passenger dendritic cell (DC) subsets in the rat liver that played a central role in the liver transplant rejection. In addition, tolerance-inducing protocol, donor-specific transfusion (DST), triggered systemic polytopical production of depleting alloantibodies to donor class I MHC antigen (DST-antibodies). METHODS:We examined the role of DST-antibodies in the trafficking of graft DC subsets and the alloresponses in a rat model. We also examined an anti-donor class II MHC (MHCII) antibody that recognizes donor DCs more selectively. RESULTS:Preoperative transfer of DST-antibodies and DST pretreatments eliminated all passenger leukocytes, including both DC subsets and depleted the sessile DCs in the graft to ~20% of control. The CD172a +CD11b/c + immunogenic subset was almost abolished. The intrahost direct or semi-direct allorecognition pathway was successfully blocked, leading to a significant suppression of the CD8 + T-cell response in the recipient lymphoid organs and the graft with delayed graft rejection. Anti-donor MHCII antibody had similar effects without temporary graft damage. Although DST pretreatment had a priming effect on the recipient Treg proliferative response, DST-primed sera and the anti-donor MHCII antibody did not. CONCLUSION:DST-antibodies and anti-donor MHCII antibodies could suppress the CD8 + T-cell-mediated liver transplant rejection by depleting donor immunogenic DCs, blocking the direct or semi-direct pathway of allorecognition. Donor MHCII-specific antibodies may be applicable as a selective suppressant of anti-donor immunity for clinical liver transplantation without the cellular damage of donor MHCII - graft cells and recipient cells. |
巻・号 | 33(5) |
ページ | 261-272 |
公開日 | 2021-4-22 |
DOI | 10.1093/intimm/dxaa076 |
PII | 6015059 |
PMID | 33258927 |
PMC | PMC8060989 |
MeSH | Animals Animals, Genetically Modified / immunology Antibody Formation / immunology Antigens, Differentiation / immunology CD11b Antigen / immunology CD8-Positive T-Lymphocytes Dendritic Cells / immunology* Graft Rejection / immunology* Graft Survival / immunology Histocompatibility Antigens Class I / immunology* Immune Tolerance / immunology Isoantibodies / immunology* Liver Transplantation / methods Rats Rats, Inbred Lew T-Lymphocytes, Regulatory / immunology Tissue Donors Transplantation, Homologous / methods |
IF | 3.519 |
リソース情報 | |
ラット | ACI/NKyo (StrainID=6) |